Influence of Catecholamines (Epinephrine/Norepinephrine) on Biofilm Formation and Adhesion in Pathogenic and Probiotic Strains of Enterococcus faecalis

Abstract

Enterococcus faecalis has controversial status due to its emerging role in nosocomial infections, while some strains with beneficial effects are used as probiotics and starter cultures in dairy industry. These bacteria can be found as resident or transient germs in the gut or on skin, where they are continually exposed to various eukaryotic molecules. In this context, the aim of our work was to evaluate the effect of the catecholamine stress hormones, epinephrine (Epi), and norepinephrine (NE) on some Enterococcus s trains. Four E. faecalis strains were included in this study: E. faecalis MMH594 and E. faecalis V583, pathogenic strains of clinical origin, E. faecalis Symbioflor 1 clone DSM 16431, a pharmaceutical probiotic, and E. faecalis OB15, a probiotic strain previously isolated from Tunisian rigouta ( Baccouri et al., 2019 ). Epi was found to modulate the formation of biofilm (biovolume and thickness) in E. faecalis , whether pathogens or probiotics. NE had less effect on biofilm formation of these bacteria. We also investigated the effect of Epi and NE on adhesion of E. faecalis to eukaryotic cells as it is the first step of colonization of the host. Epi was found to significantly enhance the adhesion of MMH594 and OB15 to Caco-2/TC7 intestinal cells and HaCaT keratinocyte cells, whereas NE significantly increased the adhesion of V583 and Symbioflor 1 DSM 16431 to Caco-2/TC7 cells, the adhesion of MMH594, Symbioflor 1 DSM 16431, and OB15 to HaCaT cells. Analysis of a putative adrenergic sensor of Epi/NE in E. faecalis , compared to QseC, the Escherichia coli adrenergic receptor, allowed the identification of VicK as the nearest protein to QseC with 29% identity and 46% similarity values. Structure modeling and molecular docking of VicK corroborated the hypothesis of possible interactions of this putative adrenergic sensor with Epi and NE, with binding energies of −4.08 and −4.49 kcal/mol, respectively. In conclusion, this study showed for the first time that stress hormones could increase biofilm formation and adhesion to eukaryotic cells in E. faecalis . Future experiments will aim to confirm by in vivo studies the role of VicK as adrenergic sensor in E. faecalis probiotic and pathogen strains. This may help to develop new strategies of antagonism/competition in the gut or skin ecological niches, and to prevent the colonization by opportunistic pathogens.

Serotonin Exposure Improves Stress Resistance, Aggregation, and Biofilm Formation in the Probiotic Enterococcus faecium NCIMB10415

“…As a matter of fact, VicR belongs to the two-component transduction system (TCS) VicKR (YycFG), previously described in E. faecalis [51]. For the same species, other authors [52] suggested its role for sensing NE and modelized it by molecular docking. In general, signal transduction plays an important role in all living organisms, but it is fundamental in bacteria, which can sense rapidly changing environmental stimuli and respond accordingly.…”

Serotonin modulates Campylobacter jejuni physiology and in vitro interaction with the gut epithelium

“…Considering the gut mucosa is a milieu of neurochemicals, not solely serotonin, further studies should assess whether the effect of serotonin on C. jejuni adhesion occurs in vivo . Indeed, catecholamine neurochemicals that are present in the gut have been reported to affect bacterial adhesion ( Cambronel et al., 2019 ; Cambronel et al., 2020 ).…”

Inter-Kingdom Signaling of Stress Hormones: Sensing, Transport and Modulation of Bacterial Physiology

“…During the same period, other alternative sensor systems for Epi/NE have been described in Salmonella such as BasRS and CpxAR (Karavolos et al, 2008(Karavolos et al, , 2011. To our knowledge, no other sensors for catecholamines have been described lately in bacteria, except two recent works on Cutibacterium acnes (former Propionibacterium acnes), and E. faecalis suggesting the role of KdpD and VicK (WalK), respectively, as putative adrenergic receptors (Borrel et al, 2019;Cambronel et al, 2020). The latter authors identified VicK as the closest protein to QseC with 29% identity and 46% similarity values.…”